Large oral doses of three ketonic solvents, 2-pentanone (PN), 2-hexanone (HX) and 2-heptanone (HP) have been shown to potentiate the hepato- and nephrotoxic action of chloroform (CHCl3) in rats. The purpose of the proposed research is to: 1) determine the minimally effective dose (MED) and a noneffective dose (NED) of each ketone in terms of ability to potentiate CHCl3 toxicity; and 2) determine the effect of repetitive administration (1 dose/day, 7 days) of the MED and NED of each ketone on CHCl3-induced liver and kidney damage. These studies will permit the applicant to determine if the potentiating capacity of multiple doses of a ketone can be predicted from studies using a single dose of ketone. The primary purpose of these experiments is to determine if the NED of of a ketone represents a threshold dose. That is, does the NED represent a dose below which repreated exposures will not result in potentiation of CHCl3, toxicity? In a second series of experiments the applicant will attempt to determine the mechanism(s) involved in ketone-induced potentiation of CHCl3 toxicity. These studies will involve determining the effect of various ketone pretreatments on the in vivo biotransformation and covalent binding of 14CHCl3.